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DPP4 dipeptidyl peptidase 4 [ Homo sapiens (human) ]

Gene ID: 1803, updated on 2-Aug-2020

Summary

Official Symbol
DPP4provided by HGNC
Official Full Name
dipeptidyl peptidase 4provided by HGNC
Primary source
HGNC:HGNC:3009
See related
Ensembl:ENSG00000197635 MIM:102720
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CD26; ADABP; ADCP2; DPPIV; TP103
Summary
The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [provided by RefSeq, Apr 2020]
Expression
Biased expression in small intestine (RPKM 70.7), placenta (RPKM 57.1) and 13 other tissues See more
Orthologs

Genomic context

See DPP4 in Genome Data Viewer
Location:
2q24.2
Exon count:
28
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (161992245..162074215, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (162848751..162931052, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 4 member 10 Neighboring gene uncharacterized LOC105373722 Neighboring gene ribulose-5-phosphate-3-epimerase pseudogene 5 Neighboring gene DPP4 promoter region Neighboring gene translocase of inner mitochondrial membrane 8A pseudogene 1 Neighboring gene DPP4 divergent transcript

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
NHGRI GWA Catalog
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
NHGRI GWA Catalog
Common variants at 12q14 and 12q24 are associated with hippocampal volume.
NHGRI GWA Catalog
Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of dipeptidyl-peptidase 4 (DPP4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env SDF-1alpha and HIV-1 gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 co-localize PubMed
env Infection of cells with Macrophage-tropic HIV-1 confers preferential survival to cells with low CD26 levels; the third hypervariable region (V3) of the HIV-1 gp120 envelope protein plays an important role in this selection process PubMed
env Although CD26 has been described as a cofactor for HIV-1 gp120 mediated entry into cells, no evidence of a CD26-gp120 interaction was observed in vitro by using glutathione S-transferase-tagged HIV-1 gp120 PubMed
env Apoptosis is observed in CD4+ cells expressing the HIV-1 gp120/gp41 complex and with enhanced levels of CD26, but is not detected in cell lines expressing an uncleavable precursor of HIV-1 gp160 PubMed
env CD26 (dipeptidyl peptidase IV) cleaves the highly conserved V3 loop of HIV-1 gp120 and functions as a cofactor for entry of HIV-1 in CD4+ human cells; coexpression of human CD4 and CD26 in murine NIH 3T3 cells renders them permissive to HIV-1 PubMed
env HIV-1 gp120 inhibits adenosine deaminase (ADA) binding to CD26 (dipeptidyl-peptidase 4) in both CD4+ and CD4- cells; this effect requires the interaction of gp120 with CD4 or CXCR4 PubMed
env Treatment of CD4+ T cells with HIV-1 gp120 significantly increases CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreases that with CD45RC PubMed
Envelope transmembrane glycoprotein gp41 env Apoptosis is observed in CD4+ cells expressing the HIV-1 gp120/gp41 complex and with enhanced levels of CD26, but is not detected in cell lines expressing an uncleavable precursor of HIV-1 gp160 PubMed
Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of dipeptidylpeptidase 4 (DPP4; CD26; adenosine deaminase complexing protein 2) in primary human brain microvascular endothelial cells PubMed
tat HIV-1 Tat induces tyrosine phosphorylation of DPPIV in Tat/DPPIV-coexpressing cells PubMed
tat HIV1-Tat co-localizes and coimmunoprecipitates with human Dipeptidyl peptidase IV (DPPIV) protein PubMed
tat The N-terminal nine amino acids of HIV-1 Tat mediate the binding of Tat to CD26 PubMed
tat HIV-1 Tat inhibits the enzymatic activity of CD26, thereby suppressing DNA synthesis and IL-1 beta production, stimulating secretion of IL-1 receptor antagonist and TNF-alpha, and causing, at least in part, the immunosuppressive effects of Tat PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
chemorepellent activity IDA
Inferred from Direct Assay
more info
PubMed 
chemorepellent activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
dipeptidyl-peptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protease binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
serine-type endopeptidase activity EXP
Inferred from Experiment
more info
PubMed 
serine-type peptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
signaling receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
virus receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
T cell costimulation IDA
Inferred from Direct Assay
more info
PubMed 
behavioral fear response IEA
Inferred from Electronic Annotation
more info
 
cell adhesion IEA
Inferred from Electronic Annotation
more info
 
endothelial cell migration IDA
Inferred from Direct Assay
more info
PubMed 
locomotory exploration behavior IEA
Inferred from Electronic Annotation
more info
 
negative chemotaxis IEA
Inferred from Electronic Annotation
more info
 
negative regulation of extracellular matrix disassembly IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of neutrophil chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
psychomotor behavior IEA
Inferred from Electronic Annotation
more info
 
regulation of cell-cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
PubMed 
regulation of insulin secretion TAS
Traceable Author Statement
more info
 
response to hypoxia IDA
Inferred from Direct Assay
more info
PubMed 
viral entry into host cell IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
apical plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
endocytic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
focal adhesion HDA PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
intercellular canaliculus IEA
Inferred from Electronic Annotation
more info
 
invadopodium membrane IDA
Inferred from Direct Assay
more info
PubMed 
lamellipodium IDA
Inferred from Direct Assay
more info
PubMed 
lamellipodium membrane IEA
Inferred from Electronic Annotation
more info
 
lysosomal membrane HDA PubMed 
membrane HDA PubMed 
membrane raft IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
dipeptidyl peptidase 4
Names
ADCP-2
DPP IV
Gly-Pro naphthylamidase
Post-proline dipeptidyl aminopeptidase IV
T-cell activation antigen CD26
Xaa-Pro-dipeptidylaminopeptidase
adenosine deaminase complexing protein 2
dipeptidyl peptidase IV
dipeptidylpeptidase 4
dipeptidylpeptidase IV (CD26, adenosine deaminase complexing protein 2)
NP_001366533.1
NP_001366534.1
NP_001366535.1
NP_001926.2

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001379604.1NP_001366533.1  dipeptidyl peptidase 4 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Conserved Domains (3) summary
    pfam00326
    Location:558762
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:107477
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam18811
    Location:3857
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region
  2. NM_001379605.1NP_001366534.1  dipeptidyl peptidase 4 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Conserved Domains (3) summary
    pfam00326
    Location:557761
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:106476
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam18811
    Location:3756
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region
  3. NM_001379606.1NP_001366535.1  dipeptidyl peptidase 4 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC008063
    Conserved Domains (3) summary
    pfam00326
    Location:541745
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:108460
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region
    pfam18811
    Location:3958
    DPPIV_rep; Dipeptidyl peptidase IV (DPP IV) low complexity region
  4. NM_001935.4NP_001926.2  dipeptidyl peptidase 4 isoform 1

    See identical proteins and their annotated locations for NP_001926.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    BC065265
    Consensus CDS
    CCDS2216.1
    UniProtKB/Swiss-Prot
    P27487
    Related
    ENSP00000353731.3, ENST00000360534.8
    Conserved Domains (3) summary
    COG1506
    Location:398764
    DAP2; Dipeptidyl aminopeptidase/acylaminoacyl peptidase [Amino acid transport and metabolism]
    pfam00326
    Location:559763
    Peptidase_S9; Prolyl oligopeptidase family
    pfam00930
    Location:108478
    DPPIV_N; Dipeptidyl peptidase IV (DPP IV) N-terminal region

RNA

  1. NR_166822.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
  2. NR_166823.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
  3. NR_166824.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063
  4. NR_166825.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008063

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    161992245..162074215 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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